微泡-脂質(zhì)體復(fù)合物

1、Paclitaxel loaded liposomes decorated with a multifunctional tandem peptide for glioma targeting cell penetrating peptides (CPP), a class of diverse short peptides widely used for siRNA, proteins and small molecular drugs delivery, also have the ability to carry drugs to penetrate BBB efficiently ，n

2、on-specific affinity to different cells, Lead to unwanted toxicity to normal brain tissues. add a selective domain to CPP or enhance the penetrating capability of specific ligands，a tandem peptide with multi functions was designed here. （This kind of tandem peptide was consisted of a specific peptid

3、e in the front position and a cell penetrating peptide in the backend so that it could possess both specific targeting and high penetrating ability.）設(shè)計(jì)思路材料 cyclic RGD c(RGDfK) and octa-arginine (R8) （以酰胺鍵連接，賴氨酸與精氨酸）Paclitaxel-liposomemicrobubble complexes as ultrasound-triggered therapeuticdrug deli

4、very carriersLMC-DOX-us已經(jīng)有人做過了，所以選擇了紫杉醇？微泡原理 將少量攜帶基因或藥物的微泡經(jīng)外周靜脈或局部注射后，微泡將少量攜帶基因或藥物的微泡經(jīng)外周靜脈或局部注射后，微泡流經(jīng)靶向部位時進(jìn)行超聲檢查，即得到超聲影像流經(jīng)靶向部位時進(jìn)行超聲檢查，即得到超聲影像。 當(dāng)當(dāng)超聲影像圖證明超聲準(zhǔn)確定位于靶向部位時，增加聲壓使之超聲影像圖證明超聲準(zhǔn)確定位于靶向部位時，增加聲壓使之達(dá)到一定強(qiáng)度，即可使微泡破裂產(chǎn)生空化效應(yīng)，空化效應(yīng)是指達(dá)到一定強(qiáng)度，即可使微泡破裂產(chǎn)生空化效應(yīng)，空化效應(yīng)是指存在于液態(tài)物質(zhì)中的微小空泡（空化核）在高強(qiáng)度超聲的作用存在于液態(tài)物質(zhì)中的微小空泡（空化核）在高強(qiáng)度

5、超聲的作用下被激發(fā)，空化核急劇膨脹和收縮直至爆裂，此過程中空化核下被激發(fā)，空化核急劇膨脹和收縮直至爆裂，此過程中空化核吸收了大量的聲能，并將能量集中釋放在極小的區(qū)域，核內(nèi)局吸收了大量的聲能，并將能量集中釋放在極小的區(qū)域，核內(nèi)局部溫度和壓力急劇升高，隨之產(chǎn)生強(qiáng)大沖擊波、內(nèi)切力、高速部溫度和壓力急劇升高，隨之產(chǎn)生強(qiáng)大沖擊波、內(nèi)切力、高速微束射流及自由基等二次效應(yīng)，不僅使微血管破裂，血管內(nèi)皮微束射流及自由基等二次效應(yīng)，不僅使微血管破裂，血管內(nèi)皮細(xì)胞收縮，細(xì)胞間隙增寬，微血管壁的通透性增大，還可使細(xì)細(xì)胞收縮，細(xì)胞間隙增寬，微血管壁的通透性增大，還可使細(xì)胞膜的完整性遭到破壞，產(chǎn)生暫時性、可逆性的小孔，增

6、加了胞膜的完整性遭到破壞，產(chǎn)生暫時性、可逆性的小孔，增加了細(xì)胞膜的通透性細(xì)胞膜的通透性 ，均能夠增強(qiáng)載藥微泡對基因或藥物的轉(zhuǎn)移，均能夠增強(qiáng)載藥微泡對基因或藥物的轉(zhuǎn)移Reversal of multidrug resistance phenotype in human breast cancer cells using doxorubicin-liposomemicrobubble complexes assisted by ultrasoundKeywordsDoxorubicin-liposomemicrobubble complexes; Multidrug resistance; Ult

7、rasound; Doxorubicin; Drug delivery 1,2 distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy (polyethylene glycol)-2000 (DSPE-PEG2000) 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC), dipalmitoylphosphatidylcholine （DPPC） 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-biotinyl(polyethylen

8、e Glycol)2000 (DSPE-PEG2000-Biotin) Perfluoropropane (C3F8 )材料 DPPC:cholesterol:DSPE-PEG-biotin in the molar ratio of 60:40:5（薄膜-透析法）2.2. Preparation of biotinylated DOX-liposomes (DL)2.3. Preparation of MBs and DOX-liposomemicrobubble complexes (DLMC)2.4. Cell cultureThe doxorubicin resistant MCF-7

9、 cell line2.5. Determination of DOX uptake and retention in DOX-resistant cells 3.8. Down regulation of P-glycoprotein protein level（wb實(shí)驗(yàn)） 3.5. Increase DNA damage in MCF-7/ADR cells 減少ROS levels in MCF-7/ADR cells Apoptosis of MCF-7/ADR induced by DLMC and US結(jié)果 由于顯著增加細(xì)胞毒性 由于復(fù)合物的優(yōu)勢，例如 1，高細(xì)胞攝取和細(xì)胞內(nèi)的快速轉(zhuǎn)運(yùn) 2，減少P糖蛋白的表達(dá)-由于DNA單鏈的斷裂 3，細(xì)胞程序性死亡的增加 more pronounced -H2AX foci staining in resistant cancer cells， indicating a more dramatic DNA damage in these resistant cells.討論逆轉(zhuǎn)多藥耐藥微泡-脂質(zhì)體治療，多藥耐藥，